TR&D 1 Summary: Adoptive cellular immunotherapy is a cancer treatment. In adoptive immunotherapy, T cells are isolated, manipulated, and stimulated in vitro, followed by expansion and administration into patients. Interest in this treatment is driven by impressive Phase I clinical trial results, in which the treatment has regressed large lesions, including treatment-resistant melanomas. The cost and complexity of treatment with adoptive immunotherapy have limited its use to research settings. In particular, T cell expansion requires prolonged culture. Autologous antigen presenting cells, or feeder cells, are a complex biologic that must be repeatedly assessed for safety and reliability, further increasing cost and labor. Immunotherapeutic strategies would benefit from effective ?off-the-shelf? expansion platforms that reduce complexity and expense. In this TR&D we will engineer and optimize nanoscale artificial Antigen Presenting Cells, nano-aAPCs coupled to simplify, streamline, and scale-up production of T cells for adoptive immunotherapy. Our proposed studies will improve production of highly efficacious tumor antigen-specific CD8+ and CD4+ T cells for ACT by effectively increasing the frequency of antigen-specific cells and their functionality due to increased control of stimulating signals.